Field of the Invention
The invention generally relates to a biosensor for the detection of nonionic molecules, macromolecules and cells and has a particular application in the detection of prostate cancer. In particular, the invention provides a dual ionophore ion-selective electrode for detecting very low levels of prostate cancer antigens.
Background
A biosensor is an analytical device which is capable of converting a biochemical signal into a quantifiable electrical signal. Biosensors typically include a biological or biologically devised sensing element in contact with a suitable transducer element. Recently, biosensors have begun to play an important role in medical research and clinical diagnosis, for example, in the detection of diabetes.
Prostate cancer is the most common cancer and one of the leading causes of cancer death among men in America. According to the Centers for Disease Control and Prevention (CDC), in 2012, 177,489 men in the United States were diagnosed with prostate cancer, and 27,244 men died from prostate cancer. Early diagnosis is crucial for patient survival.
The common methods of diagnosis for prostate cancer include prostate biopsies, transrectal ultrasounds and biomarker blood tests. However, prostate biopsies are invasive and uncomfortable, and transrectal ultrasounds sometimes have poor tissue resolution. Traditional cancer biomarker detection methods, including radioimmunoassays, enzyme-linked immunosorbent assays, electrochemical immunosorbent assays, fluorescence immunoassays, and chemiluminescence immunoassays, are widely used. However, these methods generally can only detect concentrations at or above the ng/mL level, which is insufficient for detecting very early stage cancer. Furthermore, performing methods such as ELISA and CLIA requires a secondary marker, increasing their complexity and the time needed to perform the test, and radioimmunoassays also pose a radiological hazard.
Ion-selective electrodes (ISEs; also known as specific ion electrodes, SIE), are transducers (sensors) that convert the activity of a specific ion dissolved in a solution into an electrical potential. Although they are very useful for measuring the concentration of ionic species across a membrane, extensions of their use to larger molecular species has met with limited success. While changes in signal upon the binding of a macromolecule to a ligand immobilized to a membrane can be detected, binding of the macromolecule also sterically blocks ionophore binding to the membrane, greatly decreasing the amount of signal as the measurement progresses.
There is a need to develop safer, less invasive and more accurate methods of detecting very low concentrations of prostate cancer biomarkers in order to permit the early diagnosis of prostate cancer. However, the use of conventional ISEs does not hold promise for solving this problem.